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Weight loss may be unrelated to dietary intake in the imiquimod-induced plaque psoriasis mice model

  • Jinwei Zhang , Xiaojun Yang , Hong Qiu and Wanqun Chen EMAIL logo
Published/Copyright: February 28, 2020
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Open Life Sciences
From the journal Open Life Sciences Volume 15 Issue 1

Keywords: imiquimod; plaque psoriasis; weight loss; food intake; water intake; moderate hypothermia

Since 2009, the imiquimod (IMQ)-induced mice model has been extensively adopted as a model of human plaque psoriasis to investigate the mechanisms of psoriatic pathogenesis and to verify the effective of anti-psoriatic drugs [1]. However, the side effects and the mechanism of IMQ-induced weight loss have not been investigated. Recently, we focused on some of those issues in an article which claimed that IMQ induced weight loss and decreased food intake of C57BL/6J mice in the model of generalized pustular psoriasis [2]. The difference of the two mice model between the generalized pustular psoriasis and the plaque psoriasis is the time taken to induce by IMQ. The former is induced for 4 consecutive days, while the latter is induced for 7 consecutive days. Therefore, we were interested in whether IMQ caused weight loss and the mechanism behind plaque psoriasis in the mice model.

The male BALB/mice (6–8 weeks of age) were purchased from the Center of Laboratory Animals of Southern Medical University (Guangzhou, China). The mice were randomly divided into two groups of 5-6 each.

After 1 week of adaptive feeding, the back hair (1.5×1.0 cm) of the mice was shaved. After 2 days, the two groups of mice were treated topically with vehicle (Vaseline, Lierkang Medical Technology Co., Ltd., Shandong, China; 62.5 mg per mouse) or vehicle and IMQ cream (Ming Xin Pharmaceutical Co. Ltd., Sichuan, China; 62.5 mg per mouse) on their shaved back skin for 7 consecutive days.

The psoriasis area and severity index (PASI) scores were monitored to confirm the successful establishment of plaque psoriasis. An objective scoring system was developed based on the clinical PASI to score the severity of mice skin lesion. The scaling, thickening and erythema was scored on a scale from 0 to 4 (0 represented none; 1 represented slight; 2 represented moderate; 3 represented marked; 4 represented very marked). The cumulative scores (scaling plus thickening plus erythema) served as a measure of the severity of lesions (scale 0–12). The single-blind way was used for the PASI scores. Mice on the 2nd day after IMQ induction exhibited signs of plaque psoriasis-like lesion began to appear such as scaling, thickening, erythema and the severity of lesion raised over time (Figure 1A-D). In contrast, the mice treated topically with Vaseline displayed no scaling, thickening or erythema. Those results were consistent with previous study [1] and it suggested that the mice model of plaque psoriasis was successfully established.

Figure 1 PASI scores of the mice model of plaque psoriasis. Male BALB/c mice were treated with vehicle or vehicle and IMQ cream on their shaved back skin for 7 consecutive days. Scaling (A), thickening (B), erythema (C) and cumulative (D) scores of the skin lesion. Data was shown as means±SEM (5-6 mice per group, n=3). Scaling, thickening and erythema were scored respectively on a scale from 0-4 (0, none; 1, slight; 2, moderate; 3, marked; 4, very marked). Cumulative scores were represented by scaling scores plus thickening scores plus erythema scores.
Figure 1

PASI scores of the mice model of plaque psoriasis. Male BALB/c mice were treated with vehicle or vehicle and IMQ cream on their shaved back skin for 7 consecutive days. Scaling (A), thickening (B), erythema (C) and cumulative (D) scores of the skin lesion. Data was shown as means±SEM (5-6 mice per group, n=3). Scaling, thickening and erythema were scored respectively on a scale from 0-4 (0, none; 1, slight; 2, moderate; 3, marked; 4, very marked). Cumulative scores were represented by scaling scores plus thickening scores plus erythema scores.

Subsequently, we investigated whether IMQ caused weight loss of mice in the model of plaque psoriasis. Mice were weighed by electronic scale from the 1st day to the 7th day. Results show (Figure 2A) IMQ caused weight loss of BALB/c mice from the 2nd day to the 7th day. As diet is the determining factor affecting weight, the amount of food and water intake of mice was weighed throughout the trial (We changed fresh food and water, then weigh them to calculate intake at 9 am every day). There was a reduction of food intake caused by IMQ from the 1st day to the 4th day, v-shaped, and this was most evident on the 2nd day (Figure 2B). The food intake of mice induced by IMQ tended to increase compared to the control group from the 5th day to the 7th day (Figure 2B). On the other hand, the water intake of these mice was reduced from the 1st day to the 3rd day, and was at the lowest on the 2nd day. This followed a similar to the trend of the food intake (Figure 2C). There was an increase in the water intake of mice induced by IMQ compared to the control between the 6th day to the 7th day (Figure 2C).

Figure 2 IMQ treatment causes sustained weight loss, but increased appetite after appetite loss in the mice model of plaque psoriasis. Male BALB/c mice were treated with vehicle or vehicle and IMQ cream on their shaved back skin for 7 consecutive days. Weight (A), food intake (B) and water intake (C) of the mice. Data was shown as means±SEM (5-6 mice per group, n=3) and analyzed by t-test. * represents P < 0.05, ** represents P < 0.01 and *** represents P < 0.001, compared with vehicle at individual timepoints.
Figure 2

IMQ treatment causes sustained weight loss, but increased appetite after appetite loss in the mice model of plaque psoriasis. Male BALB/c mice were treated with vehicle or vehicle and IMQ cream on their shaved back skin for 7 consecutive days. Weight (A), food intake (B) and water intake (C) of the mice. Data was shown as means±SEM (5-6 mice per group, n=3) and analyzed by t-test. * represents P < 0.05, ** represents P < 0.01 and *** represents P < 0.001, compared with vehicle at individual timepoints.

To further investigate the relationship of weight loss and food or water intake, we calculated the linear relationship between them. We found that there was no obvious relationship identified between weight loss and diet (Figure 3A and B). However, food intake was positively correlated with water intake (Figure 3C). These results suggest that weight loss in this model was independent of food and water intake. Clearly, the mechanism of weight loss was different between the model of plaque psoriasis and generalized pustular psoriasis induced by IMQ. Thus, further study is required to deduce the reason of weight loss of the mice in this model of plaque psoriasis.

Figure 3 Weight loss of the mice is independent of food or water intake in the model of plaque psoriasis. Linear relationship between weight loss and food intake (A), weight loss and water intake (B) and food intake and water intake (C). Data was shown as means±SEM (5-6 mice per group, n=3) and analyzed by corelation analyze.
Figure 3

Weight loss of the mice is independent of food or water intake in the model of plaque psoriasis. Linear relationship between weight loss and food intake (A), weight loss and water intake (B) and food intake and water intake (C). Data was shown as means±SEM (5-6 mice per group, n=3) and analyzed by corelation analyze.

We noted a case report that patients had systemic side effects when using IMQ to treat basal cell carcinoma [3]. The patient exhibited weight loss, loss of appetite, and flu-like symptoms following treatment. However, in our work we found IMQ induced BALB/c mice weight loss and increased appetite only on the 7th day. We conclude the reason behind why loss of appetite occurred in the former while an increase of appetite in the latter was due to the flu-like symptoms. Therefore, we hypothesized that body temperature may have affected the appetite of the mice. We examined the body temperature of mice from the the 1st day to the 7th day by non-contact infrared clinical thermometer (Shenzhen Ailikang Medical Co., Ltd., Shenzhen, China). The body temperature of the mice in the IMQ-induced group was significantly lower than that in the normal group from the 4th day to the 7th day (Figure 4). To further investigate the relationship of body temperature to food or water intake, we calculated the linear relationship with them. The results showed body temperature was negatively correlated with food or water intake (Figure 5A and B). Thus, it may be moderate hypothermia causing the increased appetite in order to provide more energy to the mice.

Figure 4 Body temperature of the mice. Male BALB/c mice were treated with vehicle or vehicle and IMQ cream on their shaved back skin for 7 consecutive days. Body temperature of mice from the 1st day to the 7th day was tested by non-contact infrared clinical thermometer. Data shown as means±SEM (5-6 mice per group, n=3) and analyzed by t-test. * represents P < 0.05,** represents P < 0.01,*** represents P < 0.001, compared with vehicle.
Figure 4

Body temperature of the mice. Male BALB/c mice were treated with vehicle or vehicle and IMQ cream on their shaved back skin for 7 consecutive days. Body temperature of mice from the 1st day to the 7th day was tested by non-contact infrared clinical thermometer. Data shown as means±SEM (5-6 mice per group, n=3) and analyzed by t-test. * represents P < 0.05,** represents P < 0.01,*** represents P < 0.001, compared with vehicle.

In our study we identified that in the process of IMQ-induced plaque psoriasis mice model, this resulted in decreased body weight, with the appetite of the mice decreased at first then increasing. We believe that this weight loss is independent of food or water intake. The increase in food and water intake may be because of the moderate hypothermia induced by IMQ. These findings may be of benefit to elucidate the mechanism of the mice model of plaque psoriasis.

Figure 5 Increased appetite is caused by moderate hypothermia in the model of plaque psoriasis. Linear relationship between body temperature and food intake (A) and body temperature and water intake (B). Data shown as means±SEM (5-6 mice per group, n=3) and analyzed by
Figure 5

Increased appetite is caused by moderate hypothermia in the model of plaque psoriasis. Linear relationship between body temperature and food intake (A) and body temperature and water intake (B). Data shown as means±SEM (5-6 mice per group, n=3) and analyzed by

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#These authors have contributed equally to this work.

Acknowledgements

This work was funded by National Natural Science Foundation of China (81904175), Chongqing Performance Reword Foundation (cstc2017jxj1130019), Chongqing Science and Technology Project (cstc2018jcyjAX0756) and Chongqing Health Planning Commission Project (ZY201802063).

  1. Ethical approval: The research related to animals use has been complied with all the relevant national regulations and institutional policies for the care and use of animals. All the experiments were in compliance with the National Institutes of Health Guide for the care and use of laboratory animals with the approval of Animal Care and Use Committee of Chongqing Hospital of Traditional Chinese Medicine.

  2. Conflict of interest: Authors state no conflict of interest.

References

[1] van der Fits L, Mourits S, Voerman JS, Kant M, Boon L, Laman JD, et al. Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17 axis. Journal of immunology. 2009;182:5836-5845.10.4049/jimmunol.0802999Search in Google Scholar PubMed

[2] Alvarez P, Jensen LE. Imiquimod Treatment Causes Systemic Disease in Mice Resembling Generalized Pustular Psoriasis in an IL-1 and IL-36 Dependent Manner. Mediators of inflammation. 2016:6756138.10.1155/2016/6756138Search in Google Scholar PubMed PubMed Central

[3] Hanger C, Dalrymple J, Hepburn D. Systemic side effects from topical imiquimod. The New Zealand medical journal. 2005;118:U1682.Search in Google Scholar

Received: 2019-01-22
Accepted: 2019-11-26
Published Online: 2020-02-28

© 2020 Jinwei Zhang et al. published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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https://doi.org/10.1515/biol-2020-0009
Keywords for this article
imiquimod; plaque psoriasis; weight loss; food intake; water intake; moderate hypothermia
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  72. Therapeutic effects of coronary granulocyte colony-stimulating factor on rats with chronic ischemic heart disease
  73. The effects of yam gruel on lowering fasted blood glucose in T2DM rats
  74. Circ_0084043 promotes cell proliferation and glycolysis but blocks cell apoptosis in melanoma via circ_0084043-miR-31-KLF3 axis
  75. CircSAMD4A contributes to cell doxorubicin resistance in osteosarcoma by regulating the miR-218-5p/KLF8 axis
  76. Relationship of FTO gene variations with NAFLD risk in Chinese men
  77. The prognostic and predictive value of platelet parameters in diabetic and nondiabetic patients with sudden sensorineural hearing loss
  78. LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis
  79. miR-339-3p regulated acute pancreatitis induced by caerulein through targeting TNF receptor-associated factor 3 in AR42J cells
  80. LncRNA RP1-85F18.6 affects osteoblast cells by regulating the cell cycle
  81. MiR-203-3p inhibits the oxidative stress, inflammatory responses and apoptosis of mice podocytes induced by high glucose through regulating Sema3A expression
  82. MiR-30c-5p/ROCK2 axis regulates cell proliferation, apoptosis and EMT via the PI3K/AKT signaling pathway in HG-induced HK-2 cells
  83. CTRP9 protects against MIA-induced inflammation and knee cartilage damage by deactivating the MAPK/NF-κB pathway in rats with osteoarthritis
  84. Relationship between hemodynamic parameters and portal venous pressure in cirrhosis patients with portal hypertension
  85. Long noncoding RNA FTX ameliorates hydrogen peroxide-induced cardiomyocyte injury by regulating the miR-150/KLF13 axis
  86. Ropivacaine inhibits proliferation, migration, and invasion while inducing apoptosis of glioma cells by regulating the SNHG16/miR-424-5p axis
  87. CD11b is involved in coxsackievirus B3-induced viral myocarditis in mice by inducing Th17 cells
  88. Decitabine shows anti-acute myeloid leukemia potential via regulating the miR-212-5p/CCNT2 axis
  89. Testosterone aggravates cerebral vascular injury by reducing plasma HDL levels
  90. Bioengineering and Biotechnology
  91. PL/Vancomycin/Nano-hydroxyapatite Sustained-release Material to Treat Infectious Bone Defect
  92. The thickness of surface grafting layer on bio-materials directly mediates the immuno-reacitivity of macrophages in vitro
  93. Silver nanoparticles: synthesis, characterisation and biomedical applications
  94. Food Science
  95. Bread making potential of Triticum aestivum and Triticum spelta species
  96. Modeling the effect of heat treatment on fatty acid composition in home-made olive oil preparations
  97. Effect of addition of dried potato pulp on selected quality characteristics of shortcrust pastry cookies
  98. Preparation of konjac oligoglucomannans with different molecular weights and their in vitro and in vivo antioxidant activities
  99. Animal Sciences
  100. Changes in the fecal microbiome of the Yangtze finless porpoise during a short-term therapeutic treatment
  101. Agriculture
  102. Influence of inoculation with Lactobacillus on fermentation, production of 1,2-propanediol and 1-propanol as well as Maize silage aerobic stability
  103. Application of extrusion-cooking technology in hatchery waste management
  104. In-field screening for host plant resistance to Delia radicum and Brevicoryne brassicae within selected rapeseed cultivars and new interspecific hybrids
  105. Studying of the promotion mechanism of Bacillus subtilis QM3 on wheat seed germination based on β-amylase
  106. Rapid visual detection of FecB gene expression in sheep
  107. Effects of Bacillus megaterium on growth performance, serum biochemical parameters, antioxidant capacity, and immune function in suckling calves
  108. Effects of center pivot sprinkler fertigation on the yield of continuously cropped soybean
  109. Special Issue On New Approach To Obtain Bioactive Compounds And New Metabolites From Agro-Industrial By-Products
  110. Technological and antioxidant properties of proteins obtained from waste potato juice
  111. The aspects of microbial biomass use in the utilization of selected waste from the agro-food industry
  112. Special Issue on Computing and Artificial Techniques for Life Science Applications - Part I
  113. Automatic detection and segmentation of adenomatous colorectal polyps during colonoscopy using Mask R-CNN
  114. The impedance analysis of small intestine fusion by pulse source
  115. Errata
  116. Erratum to “Diagnostic performance of serum CK-MB, TNF-α and hs-CRP in children with viral myocarditis”
  117. Erratum to “MYL6B drives the capabilities of proliferation, invasion, and migration in rectal adenocarcinoma through the EMT process”
  118. Erratum to “Thermostable cellulase biosynthesis from Paenibacillus alvei and its utilization in lactic acid production by simultaneous saccharification and fermentation”
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